Various compositions have been used to repair damaged tissues. Compositions are available to provide a scaffold to support new bone growth and/or to provide factors that induce new bone growth. Demineralized bone particles (also referred to as demineralized bone matrix or DBM) and bone morphogenetic proteins (BMPs) are two materials that have been used to enhance bone growth. For example, Jefferies (U.S. Pat. No. 4,394,370) discloses tissue repair compositions containing DBM, BMPs, or both in a reconstituted collagen matrix. Glowacki et al. (U.S. Pat. No. 4,440,750) discloses aqueous compositions of DBM and reconstituted collagen fibers.
DBM is generally composed of particles of bone tissue that have been specially treated, generally by soaking in acid, to remove their mineral content. The resulting DBM is composed mainly of highly cross-linked collagen. The remaining non-collagenous proteins include proteins such as TGF-β, PDGF, osteopontin, osteonectin, BMPs, and others. BMPs are a group of proteins categorized in the transforming growth factor beta super-family of proteins. To date, several BMPs have been isolated and associated with the bone healing process. BMPs can be isolated from bone as a mixture of proteins or produced individually through recombinant gene technology.
DBM may be used directly in bone repair compositions. See, e.g., Jefferies, supra; Glowacki et al., supra. However, in such compositions, the tissue repair factors are trapped within the highly cross-linked collagen network of the DBM. It is believed that the BMPs and other embedded tissue repair factors are slowly released as the collagen component of DBM is degraded. Therefore, the potential effectiveness of the tissue repair factors within the DBM is hindered. An alternative to slow release is to isolate the tissue repair factors from the DBM. Isolated and purified connective tissue repair factors have been used in bone repair compositions, but extraction, purification, and mixture with a dispersion medium or incorporation into a delivery vehicle requires multiple steps.
There is a need in the art for additional tissue repair compositions that employ tissue repair factors that are substantially freed of the cross-linked DBM collagen network and that do not require complicated extraction and purification steps.